In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce-PROP), for any Ce-PROP, the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shuttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.
We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce-PROP, as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce-PROP remains constant over time.
All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce-PROP, at a more pronounced level of hypnotic drug effect than intended.
Targeting Ce-PROP at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.

@article{848788,
abstract = {In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce-PROP), for any Ce-PROP, the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shuttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.
We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce-PROP, as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce-PROP remains constant over time.
All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce-PROP, at a more pronounced level of hypnotic drug effect than intended.
Targeting Ce-PROP at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.},
author = {Coppens, Marc and VAN LIMMEN, JURGEN and Schnider, Thomas and Wyler, Barbara and BONTE, SJOERT and DEWAELE, FRANK and Struys, Michel and VEREECKE, HUGO},
issn = {0007-0912},
journal = {BRITISH JOURNAL OF ANAESTHESIA},
keyword = {computerized,drug delivery,model,pharmacodynamic,pharmacokinetic,pharmacology,propofol,monitoring,depth of anaesthesia,PHARMACODYNAMICS,VOLUNTEERS,ANESTHESIA,INFUSION},
language = {eng},
number = {4},
pages = {452--458},
title = {Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic-dynamic models},
url = {http://dx.doi.org/10.1093/bja/aeq028},
volume = {104},
year = {2010},
}

Chicago

Coppens, Marc, JURGEN VAN LIMMEN, Thomas Schnider, Barbara Wyler, SJOERT BONTE, FRANK DEWAELE, Michel Struys, and HUGO VEREECKE. 2010. “Study of the Time Course of the Clinical Effect of Propofol Compared with the Time Course of the Predicted Effect-site Concentration: Performance of Three Pharmacokinetic-dynamic Models.” British Journal of Anaesthesia 104 (4): 452–458.

APA

Coppens, Marc, VAN LIMMEN, J., Schnider, T., Wyler, B., BONTE, S., DEWAELE, F., Struys, M., et al. (2010). Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic-dynamic models. BRITISH JOURNAL OF ANAESTHESIA, 104(4), 452–458.

Vancouver

1.

Coppens M, VAN LIMMEN J, Schnider T, Wyler B, BONTE S, DEWAELE F, et al. Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: performance of three pharmacokinetic-dynamic models. BRITISH JOURNAL OF ANAESTHESIA. 2010;104(4):452–8.

MLA

Coppens, Marc, JURGEN VAN LIMMEN, Thomas Schnider, et al. “Study of the Time Course of the Clinical Effect of Propofol Compared with the Time Course of the Predicted Effect-site Concentration: Performance of Three Pharmacokinetic-dynamic Models.” BRITISH JOURNAL OF ANAESTHESIA 104.4 (2010): 452–458. Print.